1. Field of the Invention
The present invention relates to optical measurement of turbid media and in particular to optical measurement tissue absorption and scattering parameters and tissue imaging.
2. Description of the Prior Art
There is considerable prior art that utilizes structured illumination to carry out fluorescence based molecular imaging in small animals. The structured nature of the illumination, which is generally presented to the target at a single spatial frequency, is used in a very simple way to inform the spatial location and topography of the surface of the illuminated target to create a three dimensional rendering of the object. Essentially the approach is a method for correcting for variations in the distance between illumination to object and object to sensor. A number of examples follow.
For a first example, as described in “Visualization Of Antitumor Treatment By Means Of Fluorescence Molecular Tomography With An Annexin V-Cy5.5 Conjugate” by Ntziachristos V, et. al. Proc Natl Acad Sci USA. 2004 Aug. 17; 101(33):12294-9. Epub 2004 Aug. 10 Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Boston, Mass. 02115, USA. vasilis@helix.mgh.harvard.edu, in vivo imaging of treatment responses at the molecular level has been recognized as potentially having a significant impact on the speed of drug discovery and ultimately to personalized medicine. There is a recognized need for developing quantitative fluorescence-based technologies with good molecular specificity and sensitivity for noninvasive 3D imaging through tissues and whole animals. Tumor response to chemotherapy can be accurately resolved by fluorescence molecular tomography (FMT) with a phosphatidylserine-sensing fluorescent probe based on modified annexins. At least a 10-fold increase of fluorochrome concentration in cyclophosphamide-sensitive tumors and a 7-fold increase of resistant tumors compared with control studies has been observed. Fluorescence molecular tomography is an optical imaging technique developed to overcome limitations of commonly used planar illumination methods and demonstrates higher quantification accuracy validated by histology. A 3-fold variation in background absorption heterogeneity may yield 100% errors in planar imaging but only 20% error in fluorescence molecular tomography, thus confirming tomographic imaging as a preferred tool for quantitative investigations of fluorescent probes in tissues. Tomographic approaches are found essential for small-animal optical imaging and are potentially well suited for clinical drug development and monitoring.”
For a second example as described in “In Vivo Tomographic Imaging Of Near-infrared Fluorescent Probes” by Ntziachristos V et. al., Mol Imaging. 2002 April-June; 1(2):82-8. Center for Molecular Imaging Research, Massachusetts General Hospital & Harvard Medical School, Bldg. 149 13th Street 5406, Charlestown, Mass. 02129-2060, USA. vasilis@helix.mgh.harvard.edu, fluorescence imaging has increasingly been used to probe protein function and gene expression in live animals. This technology is seen in the art as enhancing the study of pathogenesis, drug development, and therapeutic intervention. Three-dimensional fluorescence observations using fluorescence-mediated molecular tomography (FMT) have been developed. An imaging technique that can resolve molecular function in deep tissues by reconstructing fluorescent probe distributions in vivo has been demonstrated. Fluorescence-mediated molecular tomography findings have been compared with fluorescence reflectance imaging (FRI) to study protease function in nude mice with subsurface implanted tumors. This validation of fluorescence-mediated molecular tomography with fluorescence reflectance imaging has demonstrated the spatial congruence of fluorochrome activation as determined by the two techniques.
For a third example as disclosed in “Experimental Fluorescence Tomography Of Tissues With Noncontact Measurements” by Schulz R B et. al. IEEE Trans Med Imaging. 2004 April; 23(4):492-500 Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. r.schulz@dkfz.de, noncontact optical measurements from diffuse media has been found to facilitate the use of large detector arrays at multiple angles in diffuse optical tomography applications. Such imaging strategy eliminates the need for individual fibers in contact with tissue, restricted geometries, and matching fluids. Thus, experimental procedures and the ability to visualize functional and molecular processes in vivo is improved as shown in an experimental implementation to perform small animal imaging.
Ultrasound can be used to access subsurface information to a certain degree; however this only gives data relating to tissue mechanical properties. Optical coherence tomography is currently being developed to probe tissue subsurface structure, but can only report on very small tissue volumes. Standard photography can be performed in such a way as to provide semiquantitative information relating to surface structure, but not subsurface structure.
Fluorescence tomography approaches until recently have been limited to arrays of single sources and detectors that are serially switched in order to build up a tomographic image of the object of interest. Typically these geometries are not accommodating to a wide variety of targets. Model based approaches are required in order to extract meaning from the data.
Recently there have been efforts that employ wide field imaging and structured illumination at a single spatial frequency in order to provide an estimate of the three dimensional extent of the target of interest. Much of this work has focused on small animal imaging. Investigators have relied on the spatial distortion of the projected static illumination pattern by the surface of the object in order to “correct” for sample-to-detector variation that results from the three dimensional extent of the object of interest.
U.S. Patent Application 2003/0184757 disclosed wide field, broadband, spatially modulated illumination of turbid media. This approach has potential for simultaneous surface and sub-surface mapping of media structure, function and composition. This method can be applied with no contact to the medium over a large area, and could be used in a variety of applications that require wide-field image characterization. Numerous potential applications in the biomedical domain were indicated including those utilizing fluorescence. While quantitative modulated fluorescence imaging was mentioned in passing, a detailed illustration was not provided.